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Xenobiotica
the fate of foreign compounds in biological systems
Volume 26, 1996 - Issue 3
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Research Article

Distribution of remikiren, a potent orally active inhibitor of human renin, in laboratory animals

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Pages 243-254 | Received 20 Jul 1995, Published online: 22 Sep 2008
 

Abstract

1. Whole-body autoradiography was used to compare the distribution of remikiren in the squirrel monkey, in which the compound is a potent inhibitor of renin, with the rat and the guinea-pig in which it is less active.

2. Following intravenous administration, drug-related material was rapidly and extensively taken up by the tissues of all three species. Consistent with rapid biliary elimination, high levels of radioactivity were found in the bile duct/gail bladder/intestinal contents. Of the remaining organs, the kidney consistently showed the highest concentrations of drug-related material.

3. Radio-hplc analysis of the kidney samples demonstrated that the majority of the retained material was present as intact remikiren, even at 24 h after administration. A similar degree of retention by the kidney was also found after oral dosing.

4. Uptake of remikiren by the kidney may act as a reservoir for the drug, resulting in the prolonged duration of pharmacological activity, which, despite the high plasma clearance of the drug, has previously been observed in primates.

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